Acquired immunodeficiency syndrome (AIDS) includes a broad spectrum of clinical disorders including the recent description of central nervous system (CNS) disorders. It has been the experience of many medical centers that about 75-80% of patients with AIDS show pathologic abnormalities of the CNS. Many of these patients show no signs of other pathogens, and these cases, known as AIDS-related subacute encephalopathy, are correlated with the presence of AIDS virus in CNS tissue at autopsy. Increasingly, the earliest signs of AIDS can be detected as disorders which include dementia, spinal cord degeneration, peripheral neuropathy, hearing loss, visual loss, and other neurologic symptoms. Therefore, it is of importance to understand HIV infection in the CNS, and how this infection leads to pathologic processes resulting in CNS disorders. Recent studies by other groups have directly demonstrated the presence of human immunodeficiency virus (HIV, HTLV-III, LAV, ARV) in the CNS, including cerebrospinal fluid (CSF) and brain tissue samples. In initial studies, we have isolated genetically and biologically distinct viruses from cerebrospinal fluid and brain tissue samples of the same individual. These viruses have been characterized by gross restriction endonuclease analysis and ability to replicate in vitro in various glial and hematopoietic cell types. In the proposed studies, we will investigate these viruses further by mapping the biological phenotypes to specific genes of the viral genome. In addition, we will extend such analyses to other isolates of AIDS virus made from other individuals.